Details

Autor(en) / Beteiligte

• Zafeiriou, Maria-Patapia
• Bao, Guobin
• Hudson, James
• Halder, Rashi
• Blenkle, Alica
• Schreiber, Marie-Kristin
• Fischer, Andre
• Schild, Detlev
• Zimmermann, Wolfram-Hubertus

Titel

Developmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids

Ist Teil von

• Nature communications, 2020-07, Vol.11 (1), p.1-12, Article 3791

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• Abstract Brain organoids are promising tools for disease modeling and drug development. For proper neuronal network formation excitatory and inhibitory neurons as well as glia need to co-develop. Here, we report the directed self-organization of human induced pluripotent stem cells in a collagen hydrogel towards a highly interconnected neuronal network at a macroscale tissue format. Bioengineered Neuronal Organoids (BENOs) comprise interconnected excitatory and inhibitory neurons with supportive astrocytes and oligodendrocytes. Giant depolarizing potential (GDP)-like events observed in early BENO cultures mimic early network activity of the fetal brain. The observed GABA polarity switch and reduced GDPs in >40 day BENO indicate progressive neuronal network maturation. BENOs demonstrate expedited complex network burst development after two months and evidence for long-term potentiation. The similarity of structural and functional properties to the fetal brain may allow for the application of BENOs in studies of neuronal plasticity and modeling of disease.